This research will be a continuation of previous studies on mechanisms of teratogenesis. Attention will be focused particuarly on cell death and changed biosynthetic rates in rat embryo after treatment of pregnant dams with cytotoxic, teratogenic drugs such as hydroxyurea, cytosine arabinoside and 6-aminonicotinamide. A "split-litter" technique will be used whereby some embryos can be removed surgically within a few hours after treatment with the teratogenic drug followed by a labeled precursor, and then analyzed by histologic, biochemical or autoradiographic methods. Other offspring will be permitted to continue until day 20 of gestation when teratogenicity will be evaluated in the usual way. By comparing effects observed within a few hours after treatment with the teratologic outcome as seen on day 20 it should be possible to make valid deductions about the role of cell death and reduced biosynthesis in changing the process of differentiation and proliferation in such ways as to lead finally to the observed malformations. BIBLIOGRAPHIC REFERENCES: Scott, W.J., Ritter, E. J. and Wilson, J.G. (1975) Studies on induction of polydactyly in rats with cytosine arabinoside. Dev. Biol., 45:103-111. Ritter, E.J., Scott, W.J. and Wilon, J.G. (1975) Inhibition of ATP synthesis associated with 6-aminomicotinamide (6-AN) teratogenesis in rat embryos. Teratology, 12:233-238.